SABCS 2012

A new multigene score called EndoPredict improves on clinical measures for predicting whether estrogen receptor–positive breast cancer will metastasize, especially in the long term. The score therefore may help identify patients who can skip extended antihormonal therapy.

Investigators with the Austrian Breast and Colorectal Cancer Study Group (ABCSG) studied more than 1,700 postmenopausal patients with early estrogen receptor (ER)-positive, HER2-negative breast cancer who underwent surgery and received hormonal therapy for 5 years.

Using formalin-fixed, paraffin-embedded tumor tissue, the team derived a pretreatment EndoPredict score (Sividon Diagnostics) for each patient. The score reflects expression levels of 12 genes involved in proliferation, ER signaling, and differentiation.

Patients with a low vs. high EndoPredict score were 20%-30% more likely to be free of distant metastases during the first 5 years of follow-up and also thereafter, lead investigator Dr. Peter Dubsky reported at the San Antonio Breast Cancer Symposium.

And an EndoPredict clinical score, which combined the score with clinical features, showed even better prediction, especially in the long term: Patients having a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to remain free of distant metastases thereafter. In absolute terms, more than 98% of this low-risk group was still metastasis free at 10 years.

"The EndoPredict score identifies early and late recurrences, and offers independent prognostic information beyond what can be achieved with all common clinical parameters," Dr. Dubsky maintained.

"Why would this data be important?" he asked. "We currently have around 20,000 women included in ongoing extended/late endocrine therapy clinical trials. Speaking from our trial, ABCSG-16, also known as SALSA [Secondary Adjuvant Long-Term Study With Arimidex], we see very low event rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple," he explained. "We believe that gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice."

Dr. Laura Esserman of the University of California, San Francisco, asked how EndoPredict might stack up against other similar tools, such as the sensitivity to endocrine therapy (SET) index.

"I’d love to run this side by side in the same biomarker sample. That would be great," Dr. Dubsky commented. "We have had a fantastic presentation on the BCI (Breast Cancer Index), but this is a score that runs only in node-negative. And I think what is similar between the EndoPredict score and the BCI is that the BCI also has the ER signaling incorporated in the algorithm of genes."

Another attendee likewise asked whether the investigators had compared EndoPredict with tools such as Adjuvant Online.

"I’d be very careful with prediction power and comparing, because this is always going to depend on the biomarkers that you are using," Dr. Dubsky replied. "We have a fantastic sensitivity with this test, but how would another test from another company perform in the same biomarker sample, I cannot say."

"Would you not enrich your gene signature for late recurrence by simply examining patients who recurred late, and compare them with those that did not?" a third attendee wondered.

"The women assigned to the low-risk group have a very, very low incidence of both early and late recurrence; the high-risk group has a high risk of both early and late recurrence. The signature does in no way select specifically for the late recurrence," Dr. Dubsky explained. "I think what is special about the signature is that it can predict the late recurrences better than others do because it is not relying solely on proliferation."

Giving some background to the study, he noted, "The first-generation multigene signatures have largely been trained to predict early recurrences and not late recurrences, and commonly fail to identify the late events."

EndoPredict may be the first multigene test for breast cancer that can be used in a decentralized setting. The test has recently received the European CE mark as an in vitro diagnostic test, and is being used in Germany, Austria, and Switzerland.

The 1,702 postmenopausal women studied were participants in a pair of randomized trials (ABCSG-6 and ABCSG-8). One-third had node-positive disease. None received adjuvant chemotherapy, but all received hormonal therapy (tamoxifen alone or some sequence of tamoxifen and an aromatase inhibitor) for 5 years. Their median age was 64 years.

"This is a very homogeneously treated cohort with low to intermediate risk," Dr. Dubsky summarized.

A total of 998 women were still at risk for distant metastases after 5 years, and their median duration of follow-up was 7.1 years.

Overall, 49% of all patients had a low-risk EndoPredict score. After multivariate adjustment, these patients were significantly more likely to be free of distant metastases in the first 5 years of follow-up (hazard ratio, 1.20; P less than .001) and thereafter (HR, 1.28; P = .001). Fully 96.3% of patients with a low-risk score were metastasis free between 5 and 10 years.

"The EndoPredict is clearly an independent prognostic parameter both in the years 0 to 5 and after 5 years," Dr. Dubsky maintained.

When the C-index for discrimination was calculated, EndoPredict significantly improved on prediction of distant metastases after 5 years of follow-up when combined with the Adjuvant Online score (P less than .001) and other factors.

However, the best prediction was achieved with the predefined EndoPredict clinical score, which combined the EndoPredict score, nodal status, and tumor size, and achieved a C-index of nearly 0.8.

Fully 64% of patients still at risk for distant metastases after 5 years of follow-up had a low EndoPredict clinical score. These patients were dramatically more likely to remain free of distant metastases thereafter (HR, 5.11; P less than .001). In absolute terms, 98.2% were free of distant metastasis at 10 years.

"Risks and side effects of extended therapy should be weighed against this outcome," Dr. Dubsky recommended.

In a final analysis teasing apart the role of various genes included in the EndoPredict score, the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent positive prognostic information for late recurrence.

Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.

A new multigene score called EndoPredict improves on clinical measures for predicting whether estrogen receptor–positive breast cancer will metastasize, especially in the long term. The score therefore may help identify patients who can skip extended antihormonal therapy.

Investigators with the Austrian Breast and Colorectal Cancer Study Group (ABCSG) studied more than 1,700 postmenopausal patients with early estrogen receptor (ER)-positive, HER2-negative breast cancer who underwent surgery and received hormonal therapy for 5 years.

Using formalin-fixed, paraffin-embedded tumor tissue, the team derived a pretreatment EndoPredict score (Sividon Diagnostics) for each patient. The score reflects expression levels of 12 genes involved in proliferation, ER signaling, and differentiation.

Patients with a low vs. high EndoPredict score were 20%-30% more likely to be free of distant metastases during the first 5 years of follow-up and also thereafter, lead investigator Dr. Peter Dubsky reported at the San Antonio Breast Cancer Symposium.

And an EndoPredict clinical score, which combined the score with clinical features, showed even better prediction, especially in the long term: Patients having a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to remain free of distant metastases thereafter. In absolute terms, more than 98% of this low-risk group was still metastasis free at 10 years.

"The EndoPredict score identifies early and late recurrences, and offers independent prognostic information beyond what can be achieved with all common clinical parameters," Dr. Dubsky maintained.

"Why would this data be important?" he asked. "We currently have around 20,000 women included in ongoing extended/late endocrine therapy clinical trials. Speaking from our trial, ABCSG-16, also known as SALSA [Secondary Adjuvant Long-Term Study With Arimidex], we see very low event rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple," he explained. "We believe that gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice."

Dr. Laura Esserman of the University of California, San Francisco, asked how EndoPredict might stack up against other similar tools, such as the sensitivity to endocrine therapy (SET) index.

"I’d love to run this side by side in the same biomarker sample. That would be great," Dr. Dubsky commented. "We have had a fantastic presentation on the BCI (Breast Cancer Index), but this is a score that runs only in node-negative. And I think what is similar between the EndoPredict score and the BCI is that the BCI also has the ER signaling incorporated in the algorithm of genes."

Another attendee likewise asked whether the investigators had compared EndoPredict with tools such as Adjuvant Online.

"I’d be very careful with prediction power and comparing, because this is always going to depend on the biomarkers that you are using," Dr. Dubsky replied. "We have a fantastic sensitivity with this test, but how would another test from another company perform in the same biomarker sample, I cannot say."

"Would you not enrich your gene signature for late recurrence by simply examining patients who recurred late, and compare them with those that did not?" a third attendee wondered.

"The women assigned to the low-risk group have a very, very low incidence of both early and late recurrence; the high-risk group has a high risk of both early and late recurrence. The signature does in no way select specifically for the late recurrence," Dr. Dubsky explained. "I think what is special about the signature is that it can predict the late recurrences better than others do because it is not relying solely on proliferation."

Giving some background to the study, he noted, "The first-generation multigene signatures have largely been trained to predict early recurrences and not late recurrences, and commonly fail to identify the late events."

EndoPredict may be the first multigene test for breast cancer that can be used in a decentralized setting. The test has recently received the European CE mark as an in vitro diagnostic test, and is being used in Germany, Austria, and Switzerland.

The 1,702 postmenopausal women studied were participants in a pair of randomized trials (ABCSG-6 and ABCSG-8). One-third had node-positive disease. None received adjuvant chemotherapy, but all received hormonal therapy (tamoxifen alone or some sequence of tamoxifen and an aromatase inhibitor) for 5 years. Their median age was 64 years.

"This is a very homogeneously treated cohort with low to intermediate risk," Dr. Dubsky summarized.

A total of 998 women were still at risk for distant metastases after 5 years, and their median duration of follow-up was 7.1 years.

Overall, 49% of all patients had a low-risk EndoPredict score. After multivariate adjustment, these patients were significantly more likely to be free of distant metastases in the first 5 years of follow-up (hazard ratio, 1.20; P less than .001) and thereafter (HR, 1.28; P = .001). Fully 96.3% of patients with a low-risk score were metastasis free between 5 and 10 years.

"The EndoPredict is clearly an independent prognostic parameter both in the years 0 to 5 and after 5 years," Dr. Dubsky maintained.

When the C-index for discrimination was calculated, EndoPredict significantly improved on prediction of distant metastases after 5 years of follow-up when combined with the Adjuvant Online score (P less than .001) and other factors.

However, the best prediction was achieved with the predefined EndoPredict clinical score, which combined the EndoPredict score, nodal status, and tumor size, and achieved a C-index of nearly 0.8.

Fully 64% of patients still at risk for distant metastases after 5 years of follow-up had a low EndoPredict clinical score. These patients were dramatically more likely to remain free of distant metastases thereafter (HR, 5.11; P less than .001). In absolute terms, 98.2% were free of distant metastasis at 10 years.

"Risks and side effects of extended therapy should be weighed against this outcome," Dr. Dubsky recommended.

In a final analysis teasing apart the role of various genes included in the EndoPredict score, the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent positive prognostic information for late recurrence.

Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.

A new multigene score called EndoPredict improves on clinical measures for predicting whether estrogen receptor–positive breast cancer will metastasize, especially in the long term. The score therefore may help identify patients who can skip extended antihormonal therapy.

Investigators with the Austrian Breast and Colorectal Cancer Study Group (ABCSG) studied more than 1,700 postmenopausal patients with early estrogen receptor (ER)-positive, HER2-negative breast cancer who underwent surgery and received hormonal therapy for 5 years.

Using formalin-fixed, paraffin-embedded tumor tissue, the team derived a pretreatment EndoPredict score (Sividon Diagnostics) for each patient. The score reflects expression levels of 12 genes involved in proliferation, ER signaling, and differentiation.

Patients with a low vs. high EndoPredict score were 20%-30% more likely to be free of distant metastases during the first 5 years of follow-up and also thereafter, lead investigator Dr. Peter Dubsky reported at the San Antonio Breast Cancer Symposium.

And an EndoPredict clinical score, which combined the score with clinical features, showed even better prediction, especially in the long term: Patients having a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to remain free of distant metastases thereafter. In absolute terms, more than 98% of this low-risk group was still metastasis free at 10 years.

"The EndoPredict score identifies early and late recurrences, and offers independent prognostic information beyond what can be achieved with all common clinical parameters," Dr. Dubsky maintained.

"Why would this data be important?" he asked. "We currently have around 20,000 women included in ongoing extended/late endocrine therapy clinical trials. Speaking from our trial, ABCSG-16, also known as SALSA [Secondary Adjuvant Long-Term Study With Arimidex], we see very low event rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple," he explained. "We believe that gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice."

Dr. Laura Esserman of the University of California, San Francisco, asked how EndoPredict might stack up against other similar tools, such as the sensitivity to endocrine therapy (SET) index.

"I’d love to run this side by side in the same biomarker sample. That would be great," Dr. Dubsky commented. "We have had a fantastic presentation on the BCI (Breast Cancer Index), but this is a score that runs only in node-negative. And I think what is similar between the EndoPredict score and the BCI is that the BCI also has the ER signaling incorporated in the algorithm of genes."

Another attendee likewise asked whether the investigators had compared EndoPredict with tools such as Adjuvant Online.

"I’d be very careful with prediction power and comparing, because this is always going to depend on the biomarkers that you are using," Dr. Dubsky replied. "We have a fantastic sensitivity with this test, but how would another test from another company perform in the same biomarker sample, I cannot say."

"Would you not enrich your gene signature for late recurrence by simply examining patients who recurred late, and compare them with those that did not?" a third attendee wondered.

"The women assigned to the low-risk group have a very, very low incidence of both early and late recurrence; the high-risk group has a high risk of both early and late recurrence. The signature does in no way select specifically for the late recurrence," Dr. Dubsky explained. "I think what is special about the signature is that it can predict the late recurrences better than others do because it is not relying solely on proliferation."

Giving some background to the study, he noted, "The first-generation multigene signatures have largely been trained to predict early recurrences and not late recurrences, and commonly fail to identify the late events."

EndoPredict may be the first multigene test for breast cancer that can be used in a decentralized setting. The test has recently received the European CE mark as an in vitro diagnostic test, and is being used in Germany, Austria, and Switzerland.

The 1,702 postmenopausal women studied were participants in a pair of randomized trials (ABCSG-6 and ABCSG-8). One-third had node-positive disease. None received adjuvant chemotherapy, but all received hormonal therapy (tamoxifen alone or some sequence of tamoxifen and an aromatase inhibitor) for 5 years. Their median age was 64 years.

"This is a very homogeneously treated cohort with low to intermediate risk," Dr. Dubsky summarized.

A total of 998 women were still at risk for distant metastases after 5 years, and their median duration of follow-up was 7.1 years.

Overall, 49% of all patients had a low-risk EndoPredict score. After multivariate adjustment, these patients were significantly more likely to be free of distant metastases in the first 5 years of follow-up (hazard ratio, 1.20; P less than .001) and thereafter (HR, 1.28; P = .001). Fully 96.3% of patients with a low-risk score were metastasis free between 5 and 10 years.

"The EndoPredict is clearly an independent prognostic parameter both in the years 0 to 5 and after 5 years," Dr. Dubsky maintained.

When the C-index for discrimination was calculated, EndoPredict significantly improved on prediction of distant metastases after 5 years of follow-up when combined with the Adjuvant Online score (P less than .001) and other factors.

However, the best prediction was achieved with the predefined EndoPredict clinical score, which combined the EndoPredict score, nodal status, and tumor size, and achieved a C-index of nearly 0.8.

Fully 64% of patients still at risk for distant metastases after 5 years of follow-up had a low EndoPredict clinical score. These patients were dramatically more likely to remain free of distant metastases thereafter (HR, 5.11; P less than .001). In absolute terms, 98.2% were free of distant metastasis at 10 years.

"Risks and side effects of extended therapy should be weighed against this outcome," Dr. Dubsky recommended.

In a final analysis teasing apart the role of various genes included in the EndoPredict score, the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent positive prognostic information for late recurrence.

Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.

SAN ANTONIO – Women undergoing neoadjuvant chemotherapy for node-positive breast cancer may be able to have sentinel lymph node surgery instead of an axillary lymph node dissection, but proper surgical technique is critical for staging accuracy, a phase II trial from the American College of Surgeons Oncology Group suggests.

Among the 637 women studied in ACOSOG Z1071, all received chemotherapy and then underwent both sentinel lymph node (SLN) surgery and axillary lymph node dissection (ALND). SLN surgery correctly identified nodal status in 91.2% of cases, lead investigator Dr. Judy C. Boughey reported at the San Antonio Breast Cancer Symposium.

The false-negative rate of SLN averaged 12.6% in women with clinical N1 disease who had at least two sentinel nodes examined – slightly higher than the 10% set as a predefined endpoint. But it was lower when both blue dye and radiolabeled colloid were used to identify sentinel nodes (10.8%) and when three or more sentinel nodes were examined (9.1%).

"SLN surgery is a useful tool for detecting residual nodal disease in those women who present with node-positive breast cancer receiving neoadjuvant chemotherapy," Dr. Boughey commented in a press briefing. "Using SLN surgery in this patient population will enable us to reduce the extent of axillary surgery and therefore decrease morbidities for women treated for breast cancer."

Women were eligible for the trial if they had node-positive (T0-4, N1-2) breast cancer. After neoadjuvant chemotherapy, they underwent definitive breast surgery (lumpectomy or mastectomy), along with SLN surgery followed by a completion ALND. Patients who had N3 disease, inflammatory breast cancer, or prior ipsilateral axillary surgery were excluded.

Nodes were defined as being positive if they contained a tumor deposit measuring greater than 0.2 mm on sections stained with hematoxylin and eosin.

Sentinel nodes were identified in 92.7% of patients overall. A total of 40% of patients had no detectable nodal disease after neoadjuvant chemotherapy and thus would be unlikely to benefit from undergoing ALND, according to Dr. Boughey, a surgeon at the Mayo Clinic in Rochester, Minn.

Among the 60% of patients with detectable nodal disease (subsequently used to assess the false-negative rate of SLN), 85% had only positive sentinel nodes.

When only a single SLN was examined, the false-negative rate of SLN surgery was 31.5%, so Dr. Boughey recommends resecting a minimum of two nodes.

The false-negative rate was also lower when sentinel nodes were pathologically examined and determined to contain histologic changes (10.8%) and when a clip placed in the node at initial diagnosis was subsequently found at definitive surgery (7.4%).

"It’s important to collaborate with our radiology colleagues regarding potential for clip placement in lymph nodes, as well as our pathologists for review of sentinel lymph nodes for the presence of treatment effect," she said.

In the session where the results were presented, Dr. J. Michael Dixon of the Western General Hospital in Edinburgh asked whether a minimum of three nodes should be taken, because "if you take three or more nodes, your false-negative rate is within the range that is acceptable. Yet your conclusions said two. So I wonder if you get a second chance, you can tell us that we can do this technique if we use dual isotope and if we take three or more sentinel nodes and follow your other rules."

"We framed the conclusion based on the way the protocol had been written up front with two or more, but I think your comments are spot on," replied Dr. Boughey.

Dr. Steven Vogl of the Montefiore Medical Center in the Bronx, New York, asked about pathologic complete response (pCR).

"We did not require any specific degree of response for the patients to be in the study, since all of the patients were getting a completion ALND," Dr. Boughey replied. "We are currently evaluating specifically that question about whether the breast response and/or the nodal response on ultrasound can help define the appropriate patient population for us to tailor this therapy to."

Dr. Vogl noted that for patients who are HER2-positive, ER-negative, and triple-negative, pCR is very important. "So if we can figure out very carefully who didn’t achieve a pCR, especially in the node, we can probably do something for those patients some day with the right agents," he said.

"Do you use clips in all patients? Do you use dual agents always? And do you always remove two sentinel nodes? What is the impact of this on what we should do next?" asked session moderator Dr. Anthony Lucci Jr., of the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Boughey replied, "The take-home message is ... I’ll be looking at clip placement, making sure that we use dual-agent tracer for these cases, and ensuring that we do a thorough evaluation of the axilla and resecting any node that is radioactive, blue, or palpable.

"One of the concerns always when you are doing the sentinel node and you know you are doing a planned dissection [thereafter] is that the completeness of the evaluation of the axilla may not be quite as thorough as if you are closing as soon as you finish that sentinel node biopsy. So I think that is where the onus rests on the surgeon, so that we thoroughly evaluate the axilla and ensure this technique is as thorough as possible," she added.

In an additional analysis of patients with clinical N2 disease, the false-negative rate of SLN was 0%.

"Further work is under way regarding the secondary endpoint of this study, which will look at correlating the axillary ultrasound after chemotherapy with the false-negative rate. ... Maybe this can help improve patient selection for the procedure and further lower the false-negative rate," Dr. Boughey said. "We are also continuing to work to evaluate lymphedema rates and quality of life in these patients."

Dr. Boughey disclosed no relevant conflicts of interest.

SAN ANTONIO – Women undergoing neoadjuvant chemotherapy for node-positive breast cancer may be able to have sentinel lymph node surgery instead of an axillary lymph node dissection, but proper surgical technique is critical for staging accuracy, a phase II trial from the American College of Surgeons Oncology Group suggests.

Among the 637 women studied in ACOSOG Z1071, all received chemotherapy and then underwent both sentinel lymph node (SLN) surgery and axillary lymph node dissection (ALND). SLN surgery correctly identified nodal status in 91.2% of cases, lead investigator Dr. Judy C. Boughey reported at the San Antonio Breast Cancer Symposium.

The false-negative rate of SLN averaged 12.6% in women with clinical N1 disease who had at least two sentinel nodes examined – slightly higher than the 10% set as a predefined endpoint. But it was lower when both blue dye and radiolabeled colloid were used to identify sentinel nodes (10.8%) and when three or more sentinel nodes were examined (9.1%).

"SLN surgery is a useful tool for detecting residual nodal disease in those women who present with node-positive breast cancer receiving neoadjuvant chemotherapy," Dr. Boughey commented in a press briefing. "Using SLN surgery in this patient population will enable us to reduce the extent of axillary surgery and therefore decrease morbidities for women treated for breast cancer."

Women were eligible for the trial if they had node-positive (T0-4, N1-2) breast cancer. After neoadjuvant chemotherapy, they underwent definitive breast surgery (lumpectomy or mastectomy), along with SLN surgery followed by a completion ALND. Patients who had N3 disease, inflammatory breast cancer, or prior ipsilateral axillary surgery were excluded.

Nodes were defined as being positive if they contained a tumor deposit measuring greater than 0.2 mm on sections stained with hematoxylin and eosin.

Sentinel nodes were identified in 92.7% of patients overall. A total of 40% of patients had no detectable nodal disease after neoadjuvant chemotherapy and thus would be unlikely to benefit from undergoing ALND, according to Dr. Boughey, a surgeon at the Mayo Clinic in Rochester, Minn.

Among the 60% of patients with detectable nodal disease (subsequently used to assess the false-negative rate of SLN), 85% had only positive sentinel nodes.

When only a single SLN was examined, the false-negative rate of SLN surgery was 31.5%, so Dr. Boughey recommends resecting a minimum of two nodes.

The false-negative rate was also lower when sentinel nodes were pathologically examined and determined to contain histologic changes (10.8%) and when a clip placed in the node at initial diagnosis was subsequently found at definitive surgery (7.4%).

"It’s important to collaborate with our radiology colleagues regarding potential for clip placement in lymph nodes, as well as our pathologists for review of sentinel lymph nodes for the presence of treatment effect," she said.

In the session where the results were presented, Dr. J. Michael Dixon of the Western General Hospital in Edinburgh asked whether a minimum of three nodes should be taken, because "if you take three or more nodes, your false-negative rate is within the range that is acceptable. Yet your conclusions said two. So I wonder if you get a second chance, you can tell us that we can do this technique if we use dual isotope and if we take three or more sentinel nodes and follow your other rules."

"We framed the conclusion based on the way the protocol had been written up front with two or more, but I think your comments are spot on," replied Dr. Boughey.

Dr. Steven Vogl of the Montefiore Medical Center in the Bronx, New York, asked about pathologic complete response (pCR).

"We did not require any specific degree of response for the patients to be in the study, since all of the patients were getting a completion ALND," Dr. Boughey replied. "We are currently evaluating specifically that question about whether the breast response and/or the nodal response on ultrasound can help define the appropriate patient population for us to tailor this therapy to."

Dr. Vogl noted that for patients who are HER2-positive, ER-negative, and triple-negative, pCR is very important. "So if we can figure out very carefully who didn’t achieve a pCR, especially in the node, we can probably do something for those patients some day with the right agents," he said.

"Do you use clips in all patients? Do you use dual agents always? And do you always remove two sentinel nodes? What is the impact of this on what we should do next?" asked session moderator Dr. Anthony Lucci Jr., of the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Boughey replied, "The take-home message is ... I’ll be looking at clip placement, making sure that we use dual-agent tracer for these cases, and ensuring that we do a thorough evaluation of the axilla and resecting any node that is radioactive, blue, or palpable.

"One of the concerns always when you are doing the sentinel node and you know you are doing a planned dissection [thereafter] is that the completeness of the evaluation of the axilla may not be quite as thorough as if you are closing as soon as you finish that sentinel node biopsy. So I think that is where the onus rests on the surgeon, so that we thoroughly evaluate the axilla and ensure this technique is as thorough as possible," she added.

In an additional analysis of patients with clinical N2 disease, the false-negative rate of SLN was 0%.

"Further work is under way regarding the secondary endpoint of this study, which will look at correlating the axillary ultrasound after chemotherapy with the false-negative rate. ... Maybe this can help improve patient selection for the procedure and further lower the false-negative rate," Dr. Boughey said. "We are also continuing to work to evaluate lymphedema rates and quality of life in these patients."

Dr. Boughey disclosed no relevant conflicts of interest.

SAN ANTONIO – Women undergoing neoadjuvant chemotherapy for node-positive breast cancer may be able to have sentinel lymph node surgery instead of an axillary lymph node dissection, but proper surgical technique is critical for staging accuracy, a phase II trial from the American College of Surgeons Oncology Group suggests.

Among the 637 women studied in ACOSOG Z1071, all received chemotherapy and then underwent both sentinel lymph node (SLN) surgery and axillary lymph node dissection (ALND). SLN surgery correctly identified nodal status in 91.2% of cases, lead investigator Dr. Judy C. Boughey reported at the San Antonio Breast Cancer Symposium.

The false-negative rate of SLN averaged 12.6% in women with clinical N1 disease who had at least two sentinel nodes examined – slightly higher than the 10% set as a predefined endpoint. But it was lower when both blue dye and radiolabeled colloid were used to identify sentinel nodes (10.8%) and when three or more sentinel nodes were examined (9.1%).

"SLN surgery is a useful tool for detecting residual nodal disease in those women who present with node-positive breast cancer receiving neoadjuvant chemotherapy," Dr. Boughey commented in a press briefing. "Using SLN surgery in this patient population will enable us to reduce the extent of axillary surgery and therefore decrease morbidities for women treated for breast cancer."

Women were eligible for the trial if they had node-positive (T0-4, N1-2) breast cancer. After neoadjuvant chemotherapy, they underwent definitive breast surgery (lumpectomy or mastectomy), along with SLN surgery followed by a completion ALND. Patients who had N3 disease, inflammatory breast cancer, or prior ipsilateral axillary surgery were excluded.

Nodes were defined as being positive if they contained a tumor deposit measuring greater than 0.2 mm on sections stained with hematoxylin and eosin.

Sentinel nodes were identified in 92.7% of patients overall. A total of 40% of patients had no detectable nodal disease after neoadjuvant chemotherapy and thus would be unlikely to benefit from undergoing ALND, according to Dr. Boughey, a surgeon at the Mayo Clinic in Rochester, Minn.

Among the 60% of patients with detectable nodal disease (subsequently used to assess the false-negative rate of SLN), 85% had only positive sentinel nodes.

When only a single SLN was examined, the false-negative rate of SLN surgery was 31.5%, so Dr. Boughey recommends resecting a minimum of two nodes.

The false-negative rate was also lower when sentinel nodes were pathologically examined and determined to contain histologic changes (10.8%) and when a clip placed in the node at initial diagnosis was subsequently found at definitive surgery (7.4%).

"It’s important to collaborate with our radiology colleagues regarding potential for clip placement in lymph nodes, as well as our pathologists for review of sentinel lymph nodes for the presence of treatment effect," she said.

In the session where the results were presented, Dr. J. Michael Dixon of the Western General Hospital in Edinburgh asked whether a minimum of three nodes should be taken, because "if you take three or more nodes, your false-negative rate is within the range that is acceptable. Yet your conclusions said two. So I wonder if you get a second chance, you can tell us that we can do this technique if we use dual isotope and if we take three or more sentinel nodes and follow your other rules."

"We framed the conclusion based on the way the protocol had been written up front with two or more, but I think your comments are spot on," replied Dr. Boughey.

Dr. Steven Vogl of the Montefiore Medical Center in the Bronx, New York, asked about pathologic complete response (pCR).

"We did not require any specific degree of response for the patients to be in the study, since all of the patients were getting a completion ALND," Dr. Boughey replied. "We are currently evaluating specifically that question about whether the breast response and/or the nodal response on ultrasound can help define the appropriate patient population for us to tailor this therapy to."

Dr. Vogl noted that for patients who are HER2-positive, ER-negative, and triple-negative, pCR is very important. "So if we can figure out very carefully who didn’t achieve a pCR, especially in the node, we can probably do something for those patients some day with the right agents," he said.

"Do you use clips in all patients? Do you use dual agents always? And do you always remove two sentinel nodes? What is the impact of this on what we should do next?" asked session moderator Dr. Anthony Lucci Jr., of the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Boughey replied, "The take-home message is ... I’ll be looking at clip placement, making sure that we use dual-agent tracer for these cases, and ensuring that we do a thorough evaluation of the axilla and resecting any node that is radioactive, blue, or palpable.

"One of the concerns always when you are doing the sentinel node and you know you are doing a planned dissection [thereafter] is that the completeness of the evaluation of the axilla may not be quite as thorough as if you are closing as soon as you finish that sentinel node biopsy. So I think that is where the onus rests on the surgeon, so that we thoroughly evaluate the axilla and ensure this technique is as thorough as possible," she added.

In an additional analysis of patients with clinical N2 disease, the false-negative rate of SLN was 0%.

"Further work is under way regarding the secondary endpoint of this study, which will look at correlating the axillary ultrasound after chemotherapy with the false-negative rate. ... Maybe this can help improve patient selection for the procedure and further lower the false-negative rate," Dr. Boughey said. "We are also continuing to work to evaluate lymphedema rates and quality of life in these patients."

Dr. Boughey disclosed no relevant conflicts of interest.